Department of Orthopaedic Surgery, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul, Republic of Korea.
Department of Orthopaedic Surgery, Inha University Hospital, Incheon, Republic of Korea.
PLoS One. 2020 Sep 29;15(9):e0238024. doi: 10.1371/journal.pone.0238024. eCollection 2020.
At present, information about clinical efficacy and adverse events of controlled release (CR) form of pelubiprofen, a prodrug of 2-arylopropionic acid with relatively selective effects on cyclooxygenase-2 activity, remains scarce. In this study, we sought to determine non-inferiority of pelubiprofen CR 90 mg/day compared to aceclofenac 200 mg/day regarding clinical efficacy and adverse events after a 4-week course of medication in the patients with symptomatic knee osteoarthritis.
A total of 191 patients were randomly assigned to take either pelubiprofen CR 90 mg (n = 95) or aceclofenac 200 mg (n = 96). The primary outcome variable was non-inferiority of pain reduction between baseline and week 4 when assessed using a 100 mm pain visual analogue scale (VAS). Pelubiprofen was considered non-inferior to aceclofenac if the upper limit of the one-sided 97.5% confidence interval for the difference in terms of pain VAS was above 15 mm (the average change of pain VAS in the pelubiprofen group-pain VAS reduction in the aceclofenac group). Secondary outcome variables were the changes in 100 mm pain VAS at week 2 versus baseline, K-Western Ontario, and McMaster University Arthritis Index (K-WOMAC) changes at weeks 2 and 4 as compared to baseline, patient global assessment at weeks 2 and 4. The frequency and amount of rescue medicine usage at weeks 2 and 4 were also evaluated as the secondary outcome variable. For safety analysis, adverse events, clinical laboratory tests, vital signs, and physical examinations were assessed and conducted at each follow-up visit.
At week 4, the pain VAS values were significantly reduced in both groups receiving either pelubiprofen CR 90 mg or aceclofenac 200 mg as compared to the baseline. However, the pelubiprofen group and the aceclofenac group respectively showed the pain VAS changes of -22 and -21.9 in the pre-protocol set and -20.8 and -21.7 in the full analysis set, confirming non-inferiority. The pelubiprofen CR 90 mg showed a reduced incidence of adverse events compared to the aceclofenac 200 mg (p = 0.005).
Pelubiprofen CR 90 mg is as effective as aceclofenac 200 mg with reduced adverse events for the treatment of symptomatic knee osteoarthritis.
目前，关于普卢利布洛芬（一种对环氧化酶-2 活性具有相对选择性作用的 2-芳基丙酸前体药物）控释（CR）剂型的临床疗效和不良反应的信息仍然很少。在这项研究中，我们旨在确定普卢利布洛芬 CR 90mg/天与醋氯芬酸 200mg/天在治疗有症状的膝骨关节炎患者 4 周疗程后，在临床疗效和不良反应方面无劣效性。
共 191 例患者随机分为普卢利布洛芬 CR 90mg 组（n=95）和醋氯芬酸 200mg 组（n=96）。主要结局变量是使用 100mm 疼痛视觉模拟量表（VAS）评估从基线到第 4 周时疼痛减轻的非劣效性。如果普卢利布洛芬组疼痛 VAS 的单侧 97.5%置信区间上限大于 15mm（普卢利布洛芬组疼痛 VAS 的平均变化-醋氯芬酸组疼痛 VAS 减少），则认为普卢利布洛芬优于醋氯芬酸。次要结局变量是第 2 周和第 4 周与基线相比的 100mm 疼痛 VAS 的变化，第 2 周和第 4 周与基线相比的西部安大略省和麦克马斯特大学关节炎指数（WOMAC）的变化，第 2 周和第 4 周时患者的总体评估。第 2 周和第 4 周时的救急药物使用频率和数量也作为次要结局变量进行评估。安全性分析包括在每次随访时评估不良事件、临床实验室检查、生命体征和体格检查。
在第 4 周，接受普卢利布洛芬 CR 90mg 或醋氯芬酸 200mg 治疗的两组患者的疼痛 VAS 值均明显低于基线。然而，普卢利布洛芬组和醋氯芬酸组在预方案组中分别显示疼痛 VAS 变化为-22 和-21.9，在全分析组中分别为-20.8 和-21.7，证实了非劣效性。普卢利布洛芬 CR 90mg 的不良反应发生率低于醋氯芬酸 200mg（p=0.005）。
普卢利布洛芬 CR 90mg 与醋氯芬酸 200mg 治疗有症状的膝骨关节炎同样有效，且不良反应发生率较低。
